Home Compounds Tissue Repair & Recovery Larazotide Acetate (AT-1001)
Tissue Repair & Recovery Research Moderate Evidence

Larazotide Acetate (AT-1001)

Tight junction regulator studied for celiac disease, leaky gut, and intestinal permeability research. Competitive inhibitor of zonulin — the protein that opens intestinal tight junctions. Phase 3 trials conducted for celiac.

tight junctionleaky gutzonulinceliacintestinal permeabilitygut barrierAT-1001
Half-life
Topically active in gut lumen; minimal systemic absorption by design
SKUs
1
Evidence
Moderate Evidence

Larazotide (also known as AT-1001) is a synthetic octapeptide that has been studied primarily for celiac disease. It works by reducing intestinal permeability — specifically targeting a protein called zonulin that regulates the tight junctions between intestinal cells. It is the first compound specifically designed to address the intestinal permeability aspect of celiac disease and has completed phase 2 and phase 3 trials.

Celiac Disease Research
Larazotide has been the primary focus of multiple clinical trials in celiac disease. Phase 2 trials showed reductions in intestinal permeability and improvements in GI symptoms in patients on a gluten-free diet who continued to have symptoms. Phase 3 trials examined it as an add-on to gluten-free diet.
Intestinal Permeability Research
Larazotide targets tight junction regulation, making it an important research tool for studying how zonulin and tight junction proteins govern intestinal barrier function. This research has implications beyond celiac disease for conditions associated with elevated intestinal permeability.
Gut Barrier Biology
Beyond celiac disease, some research has examined whether larazotide's mechanism of restoring tight junctions could be relevant for other conditions involving intestinal permeability, including inflammatory bowel disease and food sensitivities.
  • Phase 2 trials in celiac disease showed reductions in intestinal permeability markers.
  • GI symptom improvements observed in patients on gluten-free diet with persistent symptoms.
  • Phase 3 trial data have been analyzed and have not shown strong efficacy on primary endpoints.
  • The intestinal permeability mechanism is well-characterized and validated as a research approach.

The phase 3 trial for celiac disease did not meet primary endpoints, which is a significant limitation for this compound's development path. While mechanistically interesting, the clinical evidence for meaningful symptom benefit in celiac disease patients is not conclusive from the phase 3 data. It is not FDA-approved for any indication.

The lining of the small intestine is made up of cells joined together by protein structures called tight junctions — think of them as seals between individual tiles. In celiac disease and some other gut conditions, these seals can be disrupted by a protein called zonulin, which is triggered by gluten and other factors. When tight junctions open, the intestinal barrier becomes more permeable, allowing partially digested food particles and bacterial products to slip through into the bloodstream and trigger immune reactions. Larazotide is designed to block the receptor that zonulin uses to signal the tight junctions to open, essentially keeping the seals closed and preventing the intestinal barrier from being compromised after a gluten exposure.

Larazotide was generally well-tolerated in clinical trials, with a side effect profile comparable to placebo in most studies. GI symptoms were the most common adverse events. It is not FDA-approved. The phase 3 data are available and suggest it is safe, though its efficacy did not reach statistical significance on primary outcomes.

Moderate Evidence

This compound has been studied in Phase 1 or Phase 2 human trials. Evidence is encouraging but more large-scale trials are needed.

Published Research Ranges
0.5–2mg three times daily oral in celiac phase 2/3 trials
Research Context Only: These are ranges reported in published scientific studies for educational reference. They are not dosing recommendations. This is not medical advice. Always consult a qualified healthcare professional.

Sources listed here are from the platform research library. All links open the original publication. No citations are generated by AI.

Larazotide Acetate for Celiac Disease: Phase 2B Trial
Gastroenterology • 2015  • DOI: 10.1053/j.gastro.2015.07.009
View Source
AT-1001 (Larazotide Acetate) Reduces Tight Junction Permeability in Celiac Disease
Gut • 2007  • DOI: 10.1136/gut.2006.100529
View Source
Larazotide Acetate for the Prevention of Gluten-Induced Symptoms in Celiac Disease
American Journal of Gastroenterology • 2016  • DOI: 10.1038/ajg.2016.71
View Source
Larazotide acetate for persistent symptoms of celiac disease despite a gluten-free diet: a randomized controlled trial
 • 2015  • DOI: 10.1053/j.gastro.2015.02.008
View Source
Larazotide acetate in patients with coeliac disease undergoing a gluten challenge: a randomised placebo-controlled study
 • 2013  • DOI: 10.1111/apt.12147
View Source
A controlled trial of gluten-free diet in patients with irritable bowel syndrome-diarrhea: effects on bowel frequency and intestinal function
 • 2013  • DOI: 10.1053/j.gastro.2013.01.049
View Source
A randomized, double-blind study of larazotide acetate to prevent the activation of celiac disease during gluten challenge
 • 2012  • DOI: 10.1038/ajg.2012.211
View Source
Is There a Future Without Gluten Restrictions for Celiac Patients? Update on Current Treatments
 • 2025  • DOI: 10.3390/nu17182960
View Source
New Therapeutic Challenges in Pediatric Gastroenterology: A Narrative Review
 • 2025  • DOI: 10.3390/healthcare13080923
View Source
Gut-liver axis in diabetes: Mechanisms and therapeutic opportunities
 • 2025  • DOI: 10.3748/wjg.v31.i29.109090
View Source
Rethinking Celiac Disease Management: Treatment Approaches Beyond the Gluten-Free Diet
 • 2025  • DOI: 10.3390/biomedicines14010029
View Source
Mechanisms of long COVID and the path toward therapeutics
 • 2024  • DOI: 10.1016/j.cell.2024.07.054
View Source
Gut-Brain Axis and Neuroinflammation: The Role of Gut Permeability and the Kynurenine Pathway in Neurological Disorders
 • 2024  • DOI: 10.1007/s10571-024-01496-z
View Source
Autoimmunity, New Potential Biomarkers and the Thyroid Gland-The Perspective of Hashimoto's Thyroiditis and Its Treatment
 • 2024  • DOI: 10.3390/ijms25094703
View Source
Zonulin as Gatekeeper in Gut-Brain Axis: Dysregulation in Glioblastoma
 • 2024  • DOI: 10.3390/biomedicines12081649
View Source
Gut-joint axis: Gut dysbiosis can contribute to the onset of rheumatoid arthritis via multiple pathways
 • 2023  • DOI: 10.3389/fcimb.2023.1092118
View Source
Zonulin as a Potential Therapeutic Target in Microbiota-Gut-Brain Axis Disorders: Encouraging Results and Emerging Questions
 • 2023  • DOI: 10.3390/ijms24087548
View Source
Relevance of biomarkers indicating gut damage and microbial translocation in people living with HIV
 • 2023  • DOI: 10.3389/fimmu.2023.1173956
View Source
Short Chain Fatty Acid Metabolism in Relation to Gut Microbiota and Genetic Variability
 • 2022  • DOI: 10.3390/nu14245361
View Source
What to do about the leaky gut
 • 2022  • DOI: 10.1136/gutjnl-2021-325428
View Source
The Intestinal Barrier Dysfunction as Driving Factor of Inflammaging
 • 2022  • DOI: 10.3390/nu14050949
View Source
Gut as an Alternative Entry Route for SARS-CoV-2: Current Evidence and Uncertainties of Productive Enteric Infection in COVID-19
 • 2022  • DOI: 10.3390/jcm11195691
View Source
Micronutrient Improvement of Epithelial Barrier Function in Various Disease States: A Case for Adjuvant Therapy
 • 2022  • DOI: 10.3390/ijms23062995
View Source
Celiac Disease and Targeting the Molecular Mechanisms of Autoimmunity in COVID Pandemic
 • 2022  • DOI: 10.3390/ijms23147719
View Source
Replacing the Burden of the Gluten Free Diet: Then, Now, and the Future
 • 2022  • DOI: 10.3390/ijms232315108
View Source
The Role of Intestinal Mucosal Barrier in Autoimmune Disease: A Potential Target
 • 2022  • DOI: 10.3389/fimmu.2022.871713
View Source
Inflammatory and Microbiota-Related Regulation of the Intestinal Epithelial Barrier
 • 2021  • DOI: 10.3389/fnut.2021.718356
View Source
Probiotics, Prebiotics and Epithelial Tight Junctions: A Promising Approach to Modulate Intestinal Barrier Function
 • 2021  • DOI: 10.3390/ijms22136729
View Source
Celiac disease in children: A review of the literature
 • 2021  • DOI: 10.5409/wjcp.v10.i4.53
View Source
Therapeutic Peptides Targeting PPI in Clinical Development: Overview, Mechanism of Action and Perspectives
 • 2021  • DOI: 10.3389/fmolb.2021.697586
View Source
Oats in the diet of children with celiac disease: preliminary results of a double-blind, randomized, placebo-controlled multicenter Italian study
 • 2013  • DOI: 10.3390/nu5114653
View Source
An overview of the role of the gut microbiota in rheumatoid arthritis
 • 2026  • DOI: 10.20517/mrr.2025.69
View Source
Intestinal Epithelial Tight Junction Barrier Regulation by Novel Pathways
 • 2025  • DOI: 10.1093/ibd/izae232
View Source
A review of gut failure as a cause and consequence of critical illness
 • 2025  • DOI: 10.1186/s13054-025-05309-7
View Source
Gluten-Free Diet and Other Celiac Disease Therapies: Current Understanding and Emerging Strategies
 • 2024  • DOI: 10.3390/nu16071006
View Source
Clinical and experimental treatment of primary humoral immunodeficiencies
 • 2024  • DOI: 10.1093/cei/uxae008
View Source
Impact of COVID-19 on Pediatric Inflammatory Bowel Diseases-From Expectations to Reality
 • 2024  • DOI: 10.3390/jpm14040399
View Source
New Developments in Celiac Disease Treatment
 • 2023  • DOI: 10.3390/ijms24020945
View Source
Immunopathogenesis and environmental triggers in coeliac disease
 • 2022  • DOI: 10.1136/gutjnl-2021-326257
View Source
The bridge of the gut-joint axis: Gut microbial metabolites in rheumatoid arthritis
 • 2022  • DOI: 10.3389/fimmu.2022.1007610
View Source
Loss of Gut Barrier Integrity In Lupus
 • 2022  • DOI: 10.3389/fimmu.2022.919792
View Source
Obstructive Sleep Apnea as a Risk Factor for COVID-19 Severity-The Gut Microbiome as a Common Player Mediating Systemic Inflammation via Gut Barrier Dysfunction
 • 2022  • DOI: 10.3390/cells11091569
View Source
Present and Future Therapeutic Approaches to Barrier Dysfunction
 • 2021  • DOI: 10.3389/fnut.2021.718093
View Source
Partners in Leaky Gut Syndrome: Intestinal Dysbiosis and Autoimmunity
 • 2021  • DOI: 10.3389/fimmu.2021.673708
View Source
The Role of Intestinal Permeability in Gastrointestinal Disorders and Current Methods of Evaluation
 • 2021  • DOI: 10.3389/fnut.2021.717925
View Source
The Effect of Bacterial Infections, Probiotics and Zonulin on Intestinal Barrier Integrity
 • 2021  • DOI: 10.3390/ijms222111359
View Source
Modulating the Blood-Brain Barrier: A Comprehensive Review
 • 2021  • DOI: 10.3390/pharmaceutics13111980
View Source
Larazotide acetate: a pharmacological peptide approach to tight junction regulation
 • 2021  • DOI: 10.1152/ajpgi.00386.2020
View Source
Intestinal Microbial Metabolites in Ankylosing Spondylitis
 • 2021  • DOI: 10.3390/jcm10153354
View Source
Gliadin Sequestration as a Novel Therapy for Celiac Disease: A Prospective Application for Polyphenols
 • 2021  • DOI: 10.3390/ijms22020595
View Source
Celiac Disease: Fallacies and Facts
 • 2021  • DOI: 10.14309/ajg.0000000000001218
View Source
Local and systemic mechanisms linking periodontal disease and inflammatory comorbidities
 • 2021  • DOI: 10.1038/s41577-020-00488-6
View Source
All disease begins in the (leaky) gut: role of zonulin-mediated gut permeability in the pathogenesis of some chronic inflammatory diseases
 • 2020  • DOI: 10.12688/f1000research.20510.1
View Source
Pathogenesis of Celiac Disease and Other Gluten Related Disorders in Wheat and Strategies for Mitigating Them
 • 2020  • DOI: 10.3389/fnut.2020.00006
View Source
The Two Faces of Wheat
 • 2020  • DOI: 10.3389/fnut.2020.517313
View Source
Noninvasive Biomarkers of Gut Barrier Function in Patients Suffering from Diarrhea Predominant-IBS: An Update
 • 2020  • DOI: 10.1155/2020/2886268
View Source
Molecular Biomarkers for Celiac Disease: Past, Present and Future
 • 2020  • DOI: 10.3390/ijms21228528
View Source
Antimicrobial Resistance in ESKAPE Pathogens
 • 2020  • DOI: 10.1128/cmr.00181-19
View Source
Celiac disease: a comprehensive current review
 • 2019  • DOI: 10.1186/s12916-019-1380-z
View Source
Intestinal Barrier Function in Gluten-Related Disorders
 • 2019  • DOI: 10.3390/nu11102325
View Source

60 sources · Platform research library · Not generated by AI

LAR1

Combination use is not endorsed - provided for research context only.

Want More Detailed Research?

Ask the AI anything about Larazotide Acetate (AT-1001) - mechanisms, trial summaries, pharmacokinetics, and comparisons.

Ask AI About Larazotide Acetate (AT-1001)
Research Education Only: This profile is for educational purposes only. All information is sourced from published scientific literature. This is not medical advice. Not for human consumption. Consult qualified medical professionals for any health decisions.